TATTON: Osimertinib plus savolitinib for patients with EGFR-mutant, MET-amplified NSCLC after progression on EGFR-TKI

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Published: 15 Apr 2019
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Prof Lecia Sequist - Massachusetts General Hospital, Boston, USA

Prof Lecia Sequist speaks to ecancer at the 2019 American Association for Cancer Research (AACR) meeting about the TATTON study looking at osimertinib plus savolitinib for patients with EGFR-mutant, MET-amplified NSCLC after progression on fist/second generation EGFR-TKI or third generation EGFR-TKI.

She reports that patients that were biomarker selected due to their MET driven resistance are responding well to the EGFR plus MET combination.

Prof Sequist informs that patients who previously received a first/second generation EGFR inhibitor (and are T790-negative and MET-positive) had a response rate of 52% compared with 25% for patients who received a third generation drug.

Read more about this research here.

At AACR this year I’m presenting results from the phase I TATTON study which is an EGFR mutant positive population progressing on their prior EGFR drug who have been found on a biopsy to have MET amplification driving the resistance. So on this study they’re treated with osimertinib, a third generation EGFR inhibitor, and savolitinib which is an oral MET inhibitor.

What has the data shown so far?

What we have seen in this interim data from the TATTON study is that these patients who are biomarker selected because of their MET driven resistance are having a nice response to the EGFR plus MET combination. The patients who have previously received a first or second generation EGFR inhibitor and are T790 negative and MET positive at the time they go into the study, their response rate is 52% with a median duration of response of around 7 months. The patients who have previously received a third generation drug, so these are typically more heavily pre-treated patients and then they developed MET driven resistance, their response rate is about 25% and median duration of response also quite durable at 9.7 months.

What are the next steps for this study?

The study is important because it shows us for the first time in a trial situation that you can effectively treat acquired resistance to EGFR inhibitors that’s driven by MET. This is the first example where we see that that’s possible and it does take an EGFR inhibitor and a MET inhibitor together to get that result. But this is a small phase I study and so the next step is to move it forward into phase II studies. Two such studies are opening in 2019, the SAVANNAH study and the ORCHARD study which will both be looking at patients who have progressed on osimertinib with MET amplification being treated with osimertinib and savolitinib.

With the combination of osimertinib and savolitinib there is a little bit more toxicity than you typically see with osimertinib alone but it was well tolerated by most of the patients. The added toxicity seems to be mostly GI related – nausea, vomiting as well as fatigue.